ABSTRACT While there is no question that experimental animal models are vital to understanding mechanisms of disease and in early-stages of drug development, there is also no shortage of examples where experimental disease models have failed to predict efficacy in human clinical trials. Veterinary clinical trials, using spontaneous animal models of human disease, accelerate successful translation and can assist in rapidly identifying ineffective treatments before progression to human clinical trials. Recent efforts from our group and the broader CTSA One Health Alliance (COHA) community have laid the ground work for integration of veterinary clinical trials into the therapeutic development pipeline by working to standardize trial processes and resources; however, a hurdle to full integration of veterinary clinical trials into the therapeutic development process remains. Presently, institutional animal care and use committees (IACUC) serve, in essence, as veterinary IRBs to review multicenter veterinary clinical trials on a site-by-site basis. Similar to the historical scenario in human medicine, site-specific protocols for approval and monitoring make harmonizing cross-institutional efforts challenging and create inefficiencies and inconsistencies that decrease rigor and reproducibility and increase time to trial completion. To address this hurdle, our proposal aims to build a streamlined platform for single IACUC review and approval of veterinary clinical trials. Building on the NCATS- driven IRB initiative, we will call this platform SMART IACUC. We hypothesize that efficiency of veterinary clinical trials can be markedly optimized and enhanced through the design and implementation of a cross-network platform for single review of multi-center veterinary clinical trials called SMART IACUC. We will test this hypothesis by first developing a collaborative platform to harmonize veterinary clinical trial review across three partner institutions, educating and training key stakeholders to ensure broad adoption and success of the developed platform across the wider COHA community, and then evaluating and refining the platform using a multi-institutional test case. Completion of the proposed work will result in uniform and seamless veterinary clinical trial approval across centers, acceptance of and engagement with the SMART IACUC process across COHA institutions and beyond, and a fully refined platform ready to be deployed as a national resource for translational research.